Staphylococcus aureus is one of the most infectious agents among staphylococcal bacteria. Currently many strains of S. aureus have developed resistance against available antibiotics. Therefore, the treatment of infections caused by them is a major challenge. During current study, desogestrel (1), a contraceptive drug, was found to be a potent growth inhibitor of drug resistant strains of S. aureus. Therefore, in search of new and effective agents against multi-drug resistant S. aureus strains, whole-cell bio-catalytic conversion of desogestrel (1) by Cunninghamella blakesleeana ATCC 8688A at pH 7.0 and 25 °C was carried out, yielding three new metabolites, 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6β,15β,17β-triol (2), 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-3β,6β,17β-triol (3), and 13-ethyl-11-methylene-18,19-dinor-17α-pregn-20-yn-3α,5α,6β,17β-tetraol (4), along with a known metabolite, 13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-6β,17β-dihydroxy-3-one (5). Among them, compounds 1–2 showed a potent activity against S. aureus EMRSA-17, S. aureus NCTC 13277 (MRSA-252), and S. aureus NCTC 13143, and clinically isolated Pakistani strain of S. aureus in an in vitro Microplate Alamar Blue Assay (MABA). Vancomycin was used as the standard drug in this assay. In addition, compound 1 also showed a significant activity against vancomycin-resistant S. aureus (VRSA) ATCC 700699. Compounds 1–5 were also evaluated against 3T3 normal cell line (mouse fibroblast) where they all were identified as non-cytotoxic. The present study thus provides new leads for the development of anti-bacterial drugs against MDR S. aureus.

金黄色葡萄球菌是葡萄球菌中最具传染性的细菌之一。目前，许多金黄色葡萄球菌菌株已对可用抗生素产生抗药性。因此，治疗由它们引起的感染是主要的挑战。在当前的研究中，发现避孕药Desogestrel（1）是金黄色葡萄球菌耐药菌株的有效生长抑制剂。因此，在寻找针对多药耐药金黄色葡萄球菌菌株的新型有效药物时，Cunninghamella blakesleeana对去氧孕烯（1）进行了全细胞生物催化转化。变种ATCC 8688a，在pH 7.0和25℃下进行，得到三个新的代谢物，13-乙基-11-亚甲基18,19 DINOR-17 α -孕-4-烯-20-炔6 β，15 β，17 β三醇（2），13-乙基-11-亚甲基18,19 DINOR-17 α -孕-4-烯-20-炔-3- β，6 β， 17 β三醇（3），和13-乙基-11-亚甲基18,19 DINOR-17 α -孕-20-炔-3- α，5 α，6 β，17 β -四醇（4），以及已知的代谢物，13-乙基-11亚甲基18,19 DINOR-17 α -孕-4-烯-20-炔6β， 17 β -二羟基-3-酮（5）。其中化合物1 - 2显示针对一个有效的活性金黄色葡萄球菌EMRSA-17，金黄色葡萄球菌NCTC 13277（MRSA-252），和金黄色葡萄球菌NCTC 13143，和临床分离的菌株巴基斯坦金黄色葡萄球菌在体外微孔板Alamar蓝分析（MABA）。万古霉素在该测定中用作标准药物。另外，化合物1也显示出对耐万古霉素的一个显著活性金黄色葡萄球菌（VRSA）ATCC 700699.化合物1 - 5还对3T3正常细胞系（小鼠成纤维细胞）进行了评估，其中它们均被鉴定为无细胞毒性。因此，本研究为抗MDR金黄色葡萄球菌的抗菌药物的开发提供了新的线索。